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AGEs mediated expression and secretion of TNF alpha in rat retinal microglia
- Source :
- Experimental Eye Research. 84:905-913
- Publication Year :
- 2007
- Publisher :
- Elsevier BV, 2007.
-
Abstract
- Diabetic retinopathy induces an inflammatory response in the retina characterized by an increase in inflammatory cytokines and the activation of microglia. The degree of microglia activation may influence the extent of retina injury following retinal metabolic stress. We have previously shown that DR rats have elevated levels of advanced glycation end products (AGEs) in their blood. We have also suggested that AGEs might be involved in microglial activation and production of tumor necrosis factor alpha (TNF alpha). In this study, we attempted to confirm that AGEs induce the release of TNF alpha from rat retinal microglia using an in vitro microglia culture system, and concurrently to explore the mediating mechanisms. AGEs increased the protein secretion and mRNA expression of TNF alpha in cultured rat retinal microglia. These effects of AGEs were primarily mediated by reactive oxygen species (ROS). Furthermore, the inhibitors for mitogen-activated protein kinases (MAPK; p38, JNK and ERK 1/2) and nuclear factor-kB (NF-kB) could significantly decrease AGEs-induced TNF alpha release. AGEs-activated microglia showed an increase of NF-kB p65 nuclear translocation. These observations indicated that pathophysiological levels of AGEs may alter rat retinal microglia function by up-regulating TNF alpha expression and release via enhanced formation of intracellular ROS. AGEs-induced ROS subsequently activates MAPK (p38, JNK and ERK1/2) and NF-kB.
- Subjects :
- Glycation End Products, Advanced
MAPK/ERK pathway
Nucleocytoplasmic Transport Proteins
medicine.medical_specialty
p38 mitogen-activated protein kinases
Biology
Antioxidants
Retina
Translocation, Genetic
Proinflammatory cytokine
Rats, Sprague-Dawley
Cellular and Molecular Neuroscience
chemistry.chemical_compound
Internal medicine
medicine
Animals
RNA, Messenger
Cells, Cultured
CD11b Antigen
Microglia
Reverse Transcriptase Polymerase Chain Reaction
Tumor Necrosis Factor-alpha
Kinase
NF-kappa B
Retinal
Sensory Systems
Neoplasm Proteins
Rats
Ophthalmology
medicine.anatomical_structure
Endocrinology
Animals, Newborn
Gene Expression Regulation
chemistry
Leukocyte Common Antigens
Tumor necrosis factor alpha
Reactive Oxygen Species
Signal Transduction
Subjects
Details
- ISSN :
- 00144835
- Volume :
- 84
- Database :
- OpenAIRE
- Journal :
- Experimental Eye Research
- Accession number :
- edsair.doi.dedup.....e40f04417f82d7a9dd53381ca02dcd6f